Total Cycle Research Articles

Reducing The Number of Intermediate Stock by Implementing Just-In-Time & Pulling System

In tire manufacturing process in PT. XYZ, there is an area called the Intermediate Area in the Building - Curing area where WIP materials are temporarily stored before proceeding to the Curing process. The capacity of Intermediate Area is 15000 pcs, and the daily production volume approximately 20000 pcs. As a result, more space in the Intermediate Area is required to accommodate the increasing tire production planning. In this study, JIT & Pull system improvement process is carried out by following the PDCA cycle methodology. The implementation of the JIT done by determining standard for the number of intermediate stocks, whereas the Pull system implementation done by setting the standard material handling cycle time standard for one cycle. To keep the improvement runs according to the plan, the guidance sheet is made as the reference of the process. These improvements done to achieve the objective which is to reduce the number of stocks in the Intermediate Area by up to 834 pcs per day and reduce the total cycle time from 110 minutes to 90 minutes. Therefore, the main contribution of this research is to reduce the number of WIP materials in intermediate area and reduce the excessive transportation in the material handling process.

Evaluation of energy performance and environmental benefits for transcritical CO2 thermal system in high-speed trains

The conventional air conditioning system used in high-speed railways has limitations in heating performance and environmental impact, necessitating the exploration of alternative refrigerants. The transcritical CO2 system has gained popularity due to its exceptional heating efficiency and environmental benefits. This study aims to evaluate the energy and environmental potentials for transcritical CO2 systems in high-speed trains based on four-vertical-and-four-horizontal railway lines within different climatic regions of China. A high-fidelity transcritical CO2 system model was first developed and validated through experiments. Then, a comprehensive energy and environmental evaluation method was proposed and applied to the four-vertical-and-four-horizontal railway lines. The results indicated that the transcritical CO2 system had a superior heating performance and competitive cooling performance based on daily and annual operations. Furthermore, the transcritical CO2 system exhibited significant environmental advantages with lower total life cycle climate performance for all lines, with an average emissions reduction ratio of 17.6% and a maximum emissions reduction ratio of 26.98%. These findings highlight the competitive energy performance and outstanding environmental benefits offered by transcritical CO2 systems as promising alternatives to air conditioning systems in railway transportation.

Life cycle costing analysis of a retrofitted hydrogen-powered locomotive: Canadian context

The transportation sector must adopt cleaner alternatives to meet global emission reduction goals and attain net-zero emissions by 2050. Hydrogen stands out as a promising solution for decarbonizing the railway sector. This study conducts an economic assessment of hydrogen locomotives, considering their entire life cycle. Life cycle costs are analyzed across various travel scenarios and life stages. For shorter distances, the operational phase and capital costs of retrofitting components contribute 64% and 21% to the total life cycle costs, respectively. In contrast, longer distances are dominated by the operational phase, representing nearly 90% of the total costs. Clean hydrogen must reduce costs to compete with diesel locomotives, as only non-sustainable hydrogen currently matches diesel operational expenses. Anticipated advancements in hydrogen technology are expected to make clean hydrogen more accessible, leading to a significant reduction in the life cycle costs of hydrogen locomotives.

ETMR-31. A UNIQUE CASE OF CNS DIFFUSE, NON-SYSTEMIC ALK+ HISTIOCYTOSIS IN A PEDIATRIC PATIENT

Abstract BACKGROUND Histiocytic disorders are a group of rare diseases with accumulation of of macrophages, monocytes, or dendritic cells in various parts of the body. ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 that is very rarely described in pediatrics. METHODS A 20 month old male presented to an adult hospital after a prolonged period of headaches, vomiting, and loss of developmental milestones. Imaging demonstrated severe hydrocephalus and extensive thickened leptomeningeal enhacement with mass effect. He underwent VP shunt placement and revision, a T7-T10 laminectomy, and tumor debulking. Extensive molecular testing, including DNA and RNA analysis by NGS was performed and a CLTC::ALK fusion was identified, along with Tier III DNA variants, yielding a diagnosis consistent with ALK-Positive Histiocytosis, with diffusivity in the CNS system. Full evaluation demonstrated no involvement of the peripheral nervous system or other systemic involvement. He initially demonstrated signs of neuro-irritation, altered tone, and lower extremity clonus. RESULTS After review of very little literature published on similar patients, although none with a clinical picture matching his, he was started on a treatment course of high dose dexamethasone, vinblastine, and lorlatinib targeting the ALK+, likely driver, mutation of his disease. On evaluation scans two months into treatment, he showed no change in his disease burden. He was transitioned to clofarabine cycles with daily lorlatinib for continued targetted therapy. After six total cycles, he demonstrated a high partial to complete remission (allowing for evidence of scarred tissue) and tremendous neurologic and developmental milestone gains. CONCLUSIONS This case demonstrates a unique presentation in which there is little described in the literature in way of clinical features or treatment standards, and further none exactly similar to this patient. After undergoing extensive evaluation and therapy modication, he responded remarkably well and continues to have optimal quality of life.

GCT-26. INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOR WITH MALIGNANT TRANSFORMATION TO EMBRYONAL RHABDOMYSARCOMA

Abstract BACKGROUND Non-germinomatous germ cell tumors (NGGCT) constitute 35%- 45% of intracranial germ cell tumors. Growing teratoma syndrome has been observed in patients with NGGCTs after starting chemotherapy. While growing teratomas are typically benign, this process can rarely involve malignant transformation and result in poor prognosis. We present the case of a patient with pineal NGGCT and growing teratoma syndrome with malignant transformation to embryonal rhabdomyosarcoma. CASE REPORT A 13-year-old male presented with headaches and vision changes. An MRI brain demonstrated a 26 x 25 x 19 mm (AP X TR X CC) mixed solid and cystic pineal mass with no evidence of metastatic disease. Due to elevated alpha fetoprotein levels in the serum and cerebrospinal fluid, he was diagnosed with intracranial NGGCT. Treatment was initiated with alternating cycles of Carboplatin/Etoposide and Ifosfamide/Etoposide. After 2 cycles of chemotherapy, a complete biochemical response was noted but MRI showed increased tumor size (presumed growing teratoma syndrome). The patient underwent complete tumor resection. Histology showed embryonal rhabdomyosarcoma as a somatic malignancy arising in a mature teratoma. Further molecular characterization revealed somatic NF1 and KRAS pathogenic mutations that are consistent with the primary diagnosis. Methylation profiling, however, did not exhibit a match with any known malignancies. Continued complete response was noted following two additional chemotherapy cycles. The patient is planned for six total chemotherapy cycles followed by high-dose craniospinal radiation with boost to the primary tumor. CONCLUSIONS Malignant transformation is a rare phenomenon in NGGCT. There is no standard of care for these patients. Further studies are needed to define ideal therapy for this patient population.

Transforming Tablet Production in Indonesia with 66% Faster Manufacturing

This study addresses the high production costs of tablet products at PT. XYZ, a pharmaceutical company in Indonesia, due to long cycle and takt times. Using Causal Branching and KATA methods, data were collected over eight months through observations, interviews, and quantitative analysis. The study achieved a 43% reduction in reject foils from destripping, a 40% decrease in total cycle time, and a 66% reduction in takt time. These results highlight effective strategies for optimizing manufacturing processes and reducing costs in the pharmaceutical industry. Highlights: Cost Reduction: 43% reject foils, 40% cycle time reduction. Methodology: Used Causal Branching and KATA for problem-solving. Data Collection: Eight-month study with observations, interviews, quantitative analysis. Keywords: Tablet production, Cycle time reduction, Takt time optimization, Causal Branching, KATA method

Stress evolution of fault-and-thrust belts in 2D numerical mechanical models

We employed numerical models to examine the dynamics of fold-and-thrust belts (FTBs), particularly focusing on the spatial and temporal interplay between stress variations and fault development. Our study explores the effects of variables such as layer thickness, basal friction, and surface diffusivity on the FTBs’ structural development, emphasizing the conditions under which frontal thrusts form. We found that fault activities within FTBs exhibit a cyclic behavior characterized by phases of initiation, quiescence, and reactivation. For over 95% of the total cycle duration, the frontal thrusts are the only active structures, and the stress within the FTB predominantly remains in a critical state. During the remaining 5%, the stress becomes over-critical, leading to the formation of a proto-thrust zone and the reactivation of pre-existing thrusts within the FTB. The lateral growth rate of FTBs is directly related to the thickness of the deforming layer, with the progression of the deformation front maintaining a steady pace across the study period. Additionally, our analysis on the progression of FTBs highlights the critical role of zonal failure spacing in determining the structural styles within FTBs. Our results indicate that narrowly spaced zonal failures, which promote the emergence of low-angle forethrusts, are more likely to occur at increased distances from the backstop. This explains the sequential frontal failure in the FTB; however, the stress accumulating at the rear weak zones also play an important role in the evolutionary patterns of the FTB. Our study offers new insights into the complex processes governing the mountain formation.

Developing a fuzzy bi-objective programming and MCDM model for bridge maintenance strategy optimization

Bridges serve as critical links in road networks, requiring continuous maintenance to ensure proper functionality throughout their lifespan. Given their pivotal role in the urban landscape, connecting various parts of a city, this research presents a multi-objective optimization model for the maintenance and repair of bridges in Babolsar, Iran. The model takes into account budget constraints and aims to minimize the total life cycle and user costs, encompassing traffic delays and vehicle expenses, while maximizing the reliability of the bridge network. Recognizing the inherent complexity of this problem, a multi-objective particle swarm optimization algorithm has been developed for an accurate solution. The study further conducts sensitivity analysis on the objective function concerning the available budget, evaluating key parameters such as hourly costs and the time value of vehicles. The results show that with an increase in the budget level, the number of repairs related to the most costly maintenance has significantly risen. In other words, as the budget expands, the model tends to favor repairs with higher costs because their impact on the bridge’s performance is more substantial.

Incidence of Rice Stem Borers in Coastal Andhra Pradesh with Emphasis on <i>Sesamia inferens</i> (Walker)

A roving survey was conducted in the rice crop grown in coastal districts of Andhra Pradesh during rabi, 2021-22 and 2022-23. Overall mean stem borer incidence varied from 13.59% - 14.83% in both the seasons. Larvae of Scirpophaga incertulas (Walker), Sesamia inferens (Walker), Chilo polychrysus (Meyers) and Chilo auricilius (Dudgeon), were recorded from four districts during the survey. Among the stem borers, S. incertulas was the most predominant species (53.37%) followed by S. inferens (44.7%). Natural larval parasitization (21%) of S. inferens by Cotesia flavipes Cameron was observed in West Godavari district. The biology of S. inferens was studied on rice cv. MTU 1121. The average larval period recorded was 32.40± 0.35 days. Total life cycle of S. inferens ranged between 41-65 and 46-73 days for male and female moths, respectively. Current study suggests that S. inferens could be a potential threat to rice cultivation in coastal Andhra Pradesh.

Effect of rituximab on remissions without minimal residual disease and immunogenicity in patients with relapsed/refractory hairy cell leukemia receiving moxetumomab pasudotox.

e19015 Background: Anti-CD22 recombinant immunotoxin moxetumomab pasudotox (Moxe) was FDA-approved for relapsed/refractory hairy cell leukemia (HCL) but is now unavailable due to vial expiration until a company resumes development. The phase 3 complete remission (CR) rate was 41%, higher in patients with lower anti-drug antibodies (ADA). Minimal residual disease (MRD) eradication led to longer CR duration. HCL and the poorer prognosis variant HCLv strongly express CD22 and CD20. A clinical trial was done to determine if Rituximab could decrease immunogenicity by killing normal B-cells in HCL patients receiving Moxe and hasten MRD-free CR by reducing HCL tumor burden. Methods: To permit Rituximab enough time to reduce ADA and tumor burden, it was administered 3 days before cycle 1 day 1 at 375 mg/m2, and Moxe was given by 30-minute infusion days 1, 3 and 5. On subsequent 28-day cycles, patients received Moxe days 1, 3 and 5, and Rituximab prior to Moxe on day 1. Patients received up to 4 cycles past MRD-free CR, or up to 8 total cycles if MRD-free CR was achieved after cycle 4. The ADA assay determined percent neutralization by serum of the cytotoxicity of Moxe on CD22+ Raji cells. Results: After 13 patients received Moxe-Rituximab (MoxeR) without dose-limiting toxicity (DLT), meeting the phase 1 endpoint, 5 additional patients received Moxe with the biosimilar Ruxience (MoxeR). The first 3 patients received Moxe at 30 mcg/Kg/dose and subsequent patients 40 mcg/Kg/dose. All 18 were evaluable for toxicity and response. Although no DLT, one patient had transient grade 3 hemolytic uremic syndrome during cycle 3 without significant symptoms or need for therapy. Of the 18 patients, 15 (83%) responded, 14 (78%) achieved CR and 13 (72%) MRD-free CR by blood and bone marrow (BM) aspirate flow cytometry and BM biopsy immunohistochemistry. MRD-free CRs included one with HCLv. Even though Moxe vial expiration prevented enrollment of the 26 planned patients needed for a 1-sided p-value <0.025 compared to Moxe alone where 30 (47%) of 64 phase 1-3 patients achieved MRD-free CR, the 53% relative improvement with MoxeR achieved a 1-sided p-value of 0.05. Compared to 29 (48%) of 61 evaluable phase 1-3 patients who received Moxe alone with high ADA levels, 4 (29%) of 18 patients had high ADA levels to MoxeR (p=0.048). At 14-51 (median 35.3) months of follow-up, all but 2 of 13 MRD-free CRs are continuing, with relapse-free survival 14-45 (median 34.5) months. Conclusions: Despite enrolling slightly fewer patients than planned, MoxeR was safe and more effective than Moxe alone at achieving MRD-free CR, probably due to lower immunogenicity and faster reduction of HCL/HCLv tumor burden. Since non-Hodgkin’s lymphoma (NHL) cells from patients are sensitive to Moxe like HCL, MoxeR could be tested after NHL treatment to convert MRD+ to MRD-free CRs. Clinical trial information: NCT03805932 .

Efficacy and safety of RP1 combined with nivolumab in patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial.

9517 Background: Patients (pts) with melanoma who progress on anti–PD-1 therapy (anti–PD-1–failed) have limited treatment options. RP1 is an HSV-1–based oncolytic immunotherapy expressing human GM-CSF and a fusogenic protein (GALV-GP-R−). Here, we present data from pts with anti–PD-1–failed melanoma, including the initial cohort and updated data from a registration-directed (R-D) cohort, from the phase 1/2 IGNYTE study (NCT03767348). Methods: Pts had locally advanced or metastatic cutaneous melanoma with ≥1 measurable and injectable tumor (≥1 cm) and confirmed progressive disease (PD) while on therapy and received anti–PD-1 ± anti–CTLA-4 therapy for ≥8 consecutive weeks, with anti–PD-1 being the last treatment received. Pts on prior adjuvant anti–PD-1 therapy had confirmed PD while on adjuvant therapy. RP1 was initially given intratumorally at 1×106 plaque-forming units (PFU)/mL and then every 2 weeks (Q2W) at 1×107 PFU/mL for up to 8 total cycles (≤10 mL/cycle) combined with nivolumab (nivo; cycles 2–8, 240 mg IV); pts then received nivo alone (240 mg Q2W or 480 mg Q4W IV) for up to 2 years, with the option to receive additional courses of RP1 if specified criteria were met. Results: Overall, 156 pts were enrolled (initial melanoma cohort, n = 16; R-D cohort, n = 140); 46.2% of pts had been treated with prior anti–PD-1 combined with anti–CTLA-4, and 51.3% of patients had stage IVM1b-d disease. The overall objective response rate (ORR) was 31.4%, and 12.2% of pts achieved complete response (CR; Table). Responses were observed irrespective of prior anti–PD-1 therapy setting and disease stage (Table). Responses were seen in uninjected lesions and in bulky and visceral disease. The ORR for pts with primary anti–PD-1 resistance was 34.1%. In pts who failed prior ipilimumab + nivo, the ORR was 26.4% (Table). The median duration of response (time from baseline to end of response for responders) was > 24 months, with 100% of responses lasting > 6 months from baseline; 78% of responses were ongoing. Treatment-related adverse events (TRAEs) associated with RP1 + nivo were predominantly grade 1–2; there was 1 grade 5 TRAE (immune-mediated myocarditis attributed to nivo). Conclusions: The updated data from this expanded cohort show that RP1 + nivo provides durable and clinically meaningful antitumor activity in pts with anti–PD-1–failed melanoma. Responses were observed in both injected and uninjected lesions, including visceral lesions. The combination continues to be well tolerated. Clinical trial information: NCT03767348 . [Table: see text]

Delay and Fairness Analysis of C-RAN for Single and Multi Scheduling Domain Strategies

Background: Centralized Radio Access Network (C-RAN) is the most promising network architecture for next-generation communication networks. It meets the need for flexibility on fronthaul as well as large bandwidth on backhaul of the network. All along, scheduling is very important for the transmission of information in an organized manner. C-RAN has not been studied with the scheduling domain strategies yet in the literature. Objective: In this work, packet transmission duration, overall transmission time, wait time, and fairness index parameters have been calculated and analysed for C-RAN architecture for two different scheduling domains. The total transmission cycle time parameter is calculated for the three upper functional split options of C-RAN. The overall transmission time is a parameter calculated for the entire uplink channel. Methods: To implement the network scenario, extensive scripting is done on MATLAB Editor for single scheduling domain (SSD) and multi-scheduling domain (MSD) for three higher functional split options of C-RAN. The data traffic generated in the network is considered random. Results: A closer examination of results reveals the advantages and disadvantages of both algorithms, as well as trade-offs between them. Conclusion: For quicker data transmission, SSD should be preferred whereas MSD should be preferred if multiple users want to access resources simultaneously. Lower functional split options of C-RAN require less transmission cycle time. The MSD technique is fairer than SSD.

Key Opinion Leaders' Interviews to Inform the Future of Benefit-Risk Planning in the Medical Total Product Life Cycle of Global Pharmaceutical and Medical Device Organizations.

Key opinion leader (KOL) interviews were conducted by the Benefit-Risk Assessment Planning(BRAP) Taskforce to seek expert opinion mainly from industry and regulatory bodies, about the current status and future direction of benefit-risk assessment (BRA) planning in the lifecycle of medical product development. The findings from these interviews are intended to help communication concerning planning for BRA between industry and regulators and shape future guidance. Key opinion leader interviews consisted of 5 questions related to BRA planning, which were administered to volunteers (mainly clinicians and statisticians) within a pool of experienced pharmaceutical and medical device professionals representing academia, industry, regulatory agenciesand a patient group. The interviewees' responses to the 5 questions were summarized. To analyze the qualitative data, a Coding System was developed to label themes arising from the interviews. The key findings from the interviews were summarized into a Master Template. A quantitative analysis based on descriptive statistics was also conducted. Of the 27 interviewees, there were 11 professionals from regulatory agencies, 11 from industry, 4 from academia and 1 from a patient advocacy group. Key findings based on the comments provided by 48% of the interviewees indicated the need of incorporating BRA into other (e.g., existing) processes with the importance of alignment between processes being stressed in the comments provided by 59% of the interviewees. Commencing BRA early in the product lifecycle was emphasized in comments provided by 44% of the interviewees. Among other needs identified were an appropriate contextualization of benefits and risks (based on comments provided by 41% of interviewees) through adoption of an integrated approach with structured support by regulatory agencies and a need for understanding the audience with better communication of benefit-risk (BR) among all stakeholders (based on comments provided by 44% of the interviewees). Almost all comments provided by interviewees (96%) highlighted the importance of utilizing patient experience/preference to guide new product development and BRA. Comments provided by 74% of the interviewees expressed the need to understand patient tolerance for risk and trade-offs, with a majority (78%) of interviewees highlighting how to gather information, and 59% stressing the need for the selection and development of appropriate methodologies as important considerations for enhancing the quality and relevance of the data collected from patients. Interviewees indicated that BRA should commence early in the medical product development and inform decision-making throughout the product lifecycle. Better planning and integration of BRA into existing processes within industry would be valuable. The importance of incorporating the patient voice into BRA and medical product development was emphasized. Other key findings from the KOL interviews included a need for improved communication of BR information, and establishment of methodologies for performing BRA and soliciting patient input.

Exposure-response analyses for optimal therapeutic dose selection of ABBV-383 in patients with relapsed/refractory multiple myeloma (RRMM).

7541 Background: ABBV-383 is a fully human, B-cell maturation antigen (BCMA) × CD3 T-cell–engaging IgG4 bispecific with an effector-silenced Fc region, 2 high-affinity BCMA- and a low-affinity CD3-binding domains. ABBV-383 monotherapy has shown promising activity in patients (pts) with RRMM (Blood 2023;142[suppl 1]:3378). Here, exposure-response (ER) analyses of efficacy and safety endpoints supporting the optimal therapeutic ABBV-383 dose selection are reported in alignment with US FDA’s Project Optimus. Methods: Efficacy (n=218) and safety (n=220) data from the phase 1 study (NCT03933735) escalation cohorts of 0.025 - 120 mg Q3W and expansion cohorts of 20, 40, 60 mg Q3W and 60 mg Q4W including objective response rate (ORR), very good partial response or better (≥VGPR), stringent complete response (sCR)/CR, adverse events (≥G3 and serious), infections (≥G3, overall and serious), cytokine release syndrome (CRS; any-grade, G1, G2, and ≥G2) were modeled. Total(unbound + bound to soluble BCMA) and free (unbound + partially bound to soluble BCMA) Cycle 1 AUCinf, Cmax, and Ctrough and population pharmacokinetic model-derived up to the time of event Cavg and avgCtrough metrics were utilized in the ER analyses (logistic regression; R Version 4.2.2). Relevant pt-specific covariates were tested. Dexamethasone premedication (36 vs 10 mg) was included in CRS models. The ER relationships were utilized to predict the probabilities of efficacy and safety endpoints for relevant doses and thereby, support justification of the optimal therapeutic dose selection. Results: Based on overall assessment, ORR, ≥VGPR, sCR/CR and ≥G3 neutropenia strongly correlated with free Cavg; CRS endpoints (any-grade CRS and G1 only CRS) strongly correlated with Cycle 1 total Cmax (p <0.05). No other endpoints had ER relationships (p >0.05). Only MM type (IgG vs Others) was selected in ≥VGPR and sCR/CR models. ER relationships suggested high response rates of >63% ORR, >53% ≥VGPR, and ≥30% sCR/CR for 40, 60 mg Q3W and 60 mg Q4W. Predictions demonstrated that 20 mg Q3W (<39% ORR and ≥VGPR; <13% sCR/CR) and untested 40 mg Q4W (<60% ORR, <45% ≥VGPR and <23% sCR/CR) provide suboptimal efficacy. The 60 mg Q4W with 36 mg dexamethasone in Cycle1 (limited follow-up and data) was predicted to have ~30% sCR/CR and 31% ≥G3 neutropenia (≈ 40 mg Q3W) and substantially lower any-grade CRS events compared with 40 and 60 mg doses with 10 mg dexamethasone in Cycle 1. Conclusions: While ER analyses indicated promising efficacy and acceptable safety profiles for 40, 60 mg Q3W, and 60 mg Q4W, they support 60 mg Q4W as the optimal ABBV-383 therapeutic dose due to its predicted better therapeutic benefit/risk profile (high response rates, improved/equivalent ≥G3 neutropenia, and lower CRS events) and extended dosing interval. ABBV-383 at 60 mg Q4W will be investigated in the registrational phase 3 trial (NCT06158841) in RRMM.

A phase II exploratory trial of adebrelimab in combination with chemotherapy and concurrent radiotherapy as a first-line treatment for oligo-metastatic extensive-stage small-cell lung cancer.

TPS8131 Background: Oligometastasis of extensive-stage small-cell lung cancer (ES-SCLC) is an intermediate state between local and extensive metastasis, characterized by reduced metastatic potential and a limited number of metastatic sites, which makes local treatment of each lesion possible. Multiple clinical studies have shown that adding local therapy to standard systemic therapy can improve the prognosis of patients with oligometastatic disease. The PD-L1 inhibitor adebrelimab combined with chemotherapy has become one of the standard regimens for first-line treatment of ES-SCLC. Based on these, we hypothesize that in patients with oligometastatic ES-SCLC at risk of early progression, the early addition of chest radiotherapy and stereotactic radiotherapy (SBRT) for metastatic lesions to first-line treatment with adebrelimab combined with chemotherapy may be expected to achieve local control, thereby improving survival benefits. Methods: This is a prospective, single-arm, multicenter, phase II exploratory trial. Patients will be eligible if they are 18 to 75 years of age; have histopathologically or cytologically confirmed ES-SCLC with the number of metastatic lesions of ≤ 5 and organ metastasis of ≤ 3 (i.e. oligometastases); have an ECOG PS of 0-1; and have no previous systemic treatment. The treatment period in this trial is subdivided into induction therapy, concurrent chemoradiotherapy, and consolidation and maintenance therapy. In the induction setting, patients will receive two 3-week cycles of adebrelimab (20 mg/kg on day 1), carboplatin (AUC of 5 mg/mL per min on day 1)/cisplatin (75 mg/m2 on day 1), and etoposide (100 mg/m2 on days 1-3). Patients who achieve partial response or stable disease after induction therapy will then receive concurrent chemoradiotherapy, of which chemotherapy regimen is the same as the induction setting. Radical IMRT radiotherapy (2.5-3 Gy/f, total dose 45-55 Gy) will be performed for the primary tumor in the chest and lymph node region, and SBRT radiotherapy will be given to metastatic lesions. Prophylactic cranial irradiation is optional. After the end of chemoradiotherapy, patients will receive 1-2 cycles of consolidation treatment with the same regimen as induction treatment, followed by adebrelimab monotherapy (20 mg/kg on day 1, q3w) as maintenance treatment until disease progression, intolerance toxicity, or up to 2 years of adebrelimab. The total cycle number of chemotherapy is 4-6. The primary endpoint is progression-free survival (PFS), and secondary endpoints are objective response rate, duration of response, overall survival (OS), 6-month and 1-year PFS rates, 1-year and 2-year OS rates, and safety. The trial is under recruitment, and a total of 62 patients are planned to be enrolled. Clinical trial information: NCT06177925 .

A retrospective study of first line atezolizumab-carboplatin-etoposide in extensive-stage small cell lung cancer: Real world data from a Spanish tertiary center.

e20100 Background: The association of immune checkpoint inhibitors (ICIs) with Platinum-Etoposide (PE) has been established as the standard treatment in extensive stage Small Cell Lung Cancer (ES-SCLC). We present a real-world analysis, conducted in a Spanish tertiary hospital, that assesses the efficacy and safety of Atezolizumab combined to Carboplatin-Etoposide (Atezo-CE) in first-line ES-SCLC treatment, based on the Impower-133 Clinical Trial (CT). Methods: In this longitudinal, retrospective study, we analysed the patients (pts) diagnosed with ES-SCLC and treated at our center from July 2020 to June 2023, comparing outcomes of PE chemotherapy and Atezo-CE regime. Primary endpoints were overall survival (OS), progression-free survival (PFS) and safety. We contrasted our findings to those obtained in trials that used different ICIs: Impower-133 (Atezolizumab), CASPIAN (Durvalumab) or KEYNOTE-604 (Pembrolizumab). Data analysis employed Chi-square, Kaplan-Meier and Log-Rank. Results: Over 35 months (m), 41 pts with ES-SCLC were treated in our center: 19 pts received PE (57.9% Cisplatin and 42.1% Carboplatin), and 22 received Atezo-CE. In the PE group: 42.1% completed 6 cycles, 21.1% 4 cycles, and 36.8% less than 4. In the Atezo-CE cohort: 81.8% completed 4 cycles, and 18.2% less than 4. Regarding Performance Status (PS) in the PE cohort vs the Atezo-PE group: PS 0 0 vs 4.5%; PS 1 47.4 vs 77.3%; PS 2 42.1 vs 18.2%; PS 3 10.5 vs 0%. Corticosteroid therapy was ongoing in 52.6% vs 50% of PE vs Atezo-CE pts, respectively, adding the ICI in later cycles without affecting total cycles of Atezo received (6.8 in our study vs 7 in the Impower-133). Adverse effects (AEs) occurred in 73.7% of PE pts vs 100% of Atezo-CE pts (68.2% chemo-induced and 31.8% immune-related). Common AEs in both groups were anemia, thrombopenia, leukopenia, asthenia and vomiting. Skin and thyroid AEs were the most frequent ICI-related. Chemotherapy dose reduction occurred in 47.4% vs 27.3% and suspension in 5.3% vs 13.3% of PE pts vs Atezo-CE pts, respectively. OS was higher in the Atezo-CE group, 11.7m (95% CI: 9.2-14.2m) compared to 6.8m (95% CI: 3.8-9.8m) in the PE cohort, p-value 0.008. PFS also favoured Atezo-CE pts, 6.9m (95% CI: 5-8.7m) vs 5m (95% CI: 2.8-7.2m) in the PE cohort, though not statistically significant, p-value 0.249. Compared to the CTs Impower-133, CASPIAN and KEYNOTE-604, which reported OS of 12.3m, 12.9m and 10.8m, respectively, and PFS of 5.2m (Impower-133) and 4.2m (KEYNOTE-604), our study with pts with worse PS and needing corticosteroids at treatment initiation (exclusion criteria in CTs), showed comparable outcomes. Conclusions: Our study underscores the importance of adding ICIs to ES-SCLC first-line treatment. It further emphasizes the need for a deeper knowledge in molecular profiling and biomarker-driven strategies to tailor ES-SCLC therapy more effectively.

Comparing the life cycle costs of a traditional and a smart HVAC control system for Australian office buildings

Many smart technologies have been introduced in buildings with the aim to reduce the energy and GHG emissions associated with their operation, particularly through improved control systems for regulating heating, ventilation and air conditioning (HVAC) equipment. Despite their energy saving potential, only a few studies have comprehensively assessed the costs associated with their practical implementation from a life cycle perspective. Accordingly, this study quantifies and compares the life cycle costs of a smart HVAC control system with that of a traditional control system, in the context of an Australian office building. For both systems, the required hardware are specified based on the characteristics of these systems and the layout of the serviced spaces in the reference building. The costs incurred over the period of assessment are quantified using the net present cost (NPC) approach. To evaluate the effects of these control systems on the operational energy costs of the building HVAC system, the control logics of both these systems are modelled through building energy simulations. The results show that, over the period of assessment, the smart control system incurred a higher total cost compared to the traditional control system. However, the findings from the simulations show that the HVAC energy cost savings achieved through the specification of the smart control system offset the additional cost incurred to deploy this system over the traditional control system. The smart control system resulted in HVAC operational cost savings between 9 % and 10 % compared to the traditional control system. Sensitivity analyses indicated that the total life cycle costs varied between −27 % and +50 %, with the discount rate and energy price increase rate being the most influential parameters.

Assessing the effectiveness of building retrofits in reducing GHG emissions: A Canadian school case study

This paper investigates the impact of energy retrofits on life cycle greenhouse gas (GHG) emissions across different electricity grid profiles in Montreal, Ottawa, and Halifax, using an existing school building as a case study. Using DesignBuilder for energy simulations and OneClick LCA for GHG emissions estimation, this study evaluates whether the reduction in the operational emission achieved by energy savings from retrofits can outweigh the increased embodied emissions from new envelope materials and equipment. In Montreal and Ottawa, where electricity is mainly generated from renewables and non-fossil fuels, retrofits involving electric heating and envelope improvements could decrease life cycle GHG emissions by up to 75 %. However, if the building initially used electric heating, the retrofits led to an increase in life cycle carbon emissions by 170 % in Montreal and 56 % in Ottawa, respectively, due to the embodied emissions of retrofit materials and equipment. In Halifax, where the electricity grid relies heavily on fossil fuels, all retrofit scenarios showed a positive impact on GHG reductions. Enhancing the building envelope and transitioning from natural gas to electric heating slightly reduced total emissions by 4 %, but retaining natural gas heating decreased the total life cycle GHG emissions by 27 %. This study emphasizes the importance of a comprehensive life cycle assessment in developing policies for achieving carbon neutrality. It demonstrates that the effectiveness of retrofits in reducing GHG emissions significantly depends on the local energy grid, suggesting tailored approaches based on regional energy profiles to optimize emission reductions and energy efficiency.

Population Dynamics of <i>Helicoverpa Armigera</i> (Hubner) in Chickpea

A field experiment was carried out to study the population dynamics and bionomics of gram pod borer Helicoverpa armigera (Hubner) in chickpea at Agronomy farm and laboratory, S K N College of Agriculture, Jobner, Jaipur (Rajasthan) during rabi 2021-22. The data revealed that the first appearance was in 50th standard meteorological week (SMW) and attained peak in 8th SMW. Statistical analysis of weather parameters with larval incidence showed significant positive correlation only with maximum temperature (r = 0.56*). The biological traits of H. armigera has been studied at 20± 1°C coupled with 60± 5% RH and 12 L: 12 D photoperiod in the laboratory revealed that the single female produced 445.25± 50.02 eggs; incubation period ranged from 3.92± 0.81 days; hatchability was 78.611± 9.73%; larvae passed through five instars and total larval duration lasted 12 to 21 days; pupal stage varied from 10 to 17 days; and total life cycle took 44 to 66 days; longevity of male and female moths varied from 5.42± 1.28 and 8.52± 1.72 days, respectively.

Optimization of off-grid hybrid renewable energy systems for cost-effective and reliable power supply in Gaita Selassie Ethiopia

This paper explores scenarios for powering rural areas in Gaita Selassie with renewable energy plants, aiming to reduce system costs by optimizing component numbers to meet energy demands. Various scenarios, such as combining solar photovoltaic (PV) with pumped hydro-energy storage (PHES), utilizing wind energy with PHES, and integrating a hybrid system of PV, wind, and PHES, have been evaluated based on diverse criteria, encompassing financial aspects and reliability. To achieve the results, meta-heuristics such as the Multiobjective Gray wolf optimization algorithm (MOGWO) and Multiobjective Grasshopper optimization algorithm (MOGOA) were applied using MATLAB software. Moreover, optimal component sizing has been investigated utilizing real-time assessment data and meteorological data from Gaita Sillasie, Ethiopia. Metaheuristic optimization techniques were employed to pinpoint the most favorable loss of power supply probability (LPSP) with the least cost of energy (COE) and total life cycle cost (TLCC) for the hybrid system, all while meeting operational requirements in various scenarios. The Multi-Objective Grey Wolf Optimization (MOGWO) technique outperformed the Multi-Objective Grasshopper Optimization Algorithm (MOGOA) in optimizing the problem, as suggested by the results. Furthermore, based on MOGWO findings, the hybrid solar PV-Wind-PHES system demonstrated the lowest COE (0.126€/kWh) and TLCC (€6,897,300), along with optimal satisfaction of the village's energy demand and LPSP value. In the PV-Wind-PHSS scenario, the TLCC and COE are 38%, 18%, 2%, and 1.5% lower than those for the Wind-PHS and PV-PHSS scenarios at LPSP 0%, according to MOGWO results. Overall, this research contributes valuable insights into the design and implementation of sustainable energy solutions for remote communities, paving the way for enhanced energy access and environmental sustainability.